Category: DrugDesign

We are in the era with 100,000 protein structures available. Now we need to analyse what the crystallographic community already have rather than predicting probes in the vacuum.

When you know the ligand is bound inside the identifiable PDB crystal structure, it is surely affect that protein and we showed you the associated Ki from peer-review literature. So that is how we build the bridge from structures to precision medicine.

The residues that you want to fish out from the multiple alignment conservation may be there but may not be a must. The atoms that must be there are atoms that stay there and pair up with the ligand most of the time. The residues that causes the change in binding affinities is what you want to fish for selectivity.

What the drug community need is perhaps a linker such as MANORAA to go all the way from ligands to proteins, pathways, SNPs and target human organs plus a bit of help from the collaborative effort from various disciplines.

It is the very first attempt that ligand structures can complement the drug discovery pipeline with mostly experimental data source support to the expression levels.

It works on your phone, tablet, mac and PC so I can browse my drug on the go.

Its ligand superposition function allows you to make programmable code for fragments superposition on the URL so your drug fragment remains anonymous.

This is a screenshot from my webservice MAHORI. The service has an aim to assist fragment-based inhibitor design. It is a bit complicate to use and therefore I create a video from a screen capturing program.

The idea is that similar chemical fragments in the binding pocket of proteins should make contact to similar atomic environment. If you choose the set of hetero-atoms that can influence the binding, you will find that they form similar numbers of interactions in various pockets.

The example illustrates the use of staurosporine’s N4 and O6 atoms, which forms similar number of interactions among various kinases. If you have a fragment of interest, you can put those fragments to look for the existing environment in the Protein Data Bank. Maybe those outputs resemble your pocket of interest.

Much easier is this Link here, Multi-target Design, at SlideBoom. It is better for viewing on the internet.

Of course, I did not make it for my public talk as my good old friend once gave me a comment after enjoying a good laugh at it. He said “You will regret it, Wi”. So I chuck this out from the summer seminar slides that term.

If you enjoy it, please click like or give me a shout.

Let’s see how it goes…

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Ajarn Wi

I'm a lecturer living in Bangkok. I love to work at the interface between Art & Science.